simultaneous hyperpolarized [1-13c]pyruvate and 18f-fdg pet/mrs in cancer patients

Conditions: Breast Cancer; Neuroendocrine Tumors; Neuroendocrine Carcinoma; Neuroendocrine Carcinoma Metastatic; Lymphoma; Sarcoma

Summary: prospective phase 2a clinical trial to demonstrate proof-of-concept for simultaneous hyperpolarized \[1-13c\]pyruvate and 18f-fdg for positron emission tomography (pet) and mrs (magnetic resonance spectroscopy) in a pet/mr scanner in patients with cancer.

pet imaging with 18f-fdg is a well established method for non invasively assessing the intracellular glucose accumulation. 18f-fdg pet is used in many applications with diagnosing and staging of patients with cancer being one of the primary indications. once internalized into the cell, 18f-fdg is phosphorylated to the metabolically inactive 18f-fdg-6-phosphate. therefore it is not possible to determine what happens to the downstream glucose metabolites. in particular, it is not possible to determine the conversion into lactate, which is upregulated in many cancers. the upregulation of lactate conversion in cancers, even in presence of oxygen, is known as the warburg effect. hyperpolarized \[1-13c\]pyruvate mrs makes is possible to circumvent this limitation. the technique makes is it possible to follow the downstream fate of the glycolysis intermediate, pyruvate, and in particular makes is is possible to non-invasively and in in real time measure the glycolytic conversion of pyruvate into lactate as a direct measure of the warburg effect. when using a pet/mr scanner, it is possible to simultaneous measure the glucose influx with 18f-fdg and the conversion of pyruvate into lactate with hyperpolarized \[1-13c\]pyruvate. in this way, the two modalities provide complementary information on the in vivo glycose metabolism. the prospective phase 2a project will include up to 15 patients diagnosed with breast cancer, gastro-entero-pancreatic neuroendocrine neoplasms (gep-nen) of all grades (g1, g2, g3)., lymphomas or sarcomas the aim is to demonstrate proof-of-concept for the feasibility of simultaneous acquisition of hyperpolarized \[1-13c\]pyruvate mrs and 18f-fdg pet imaging in a pet/mr scanner in cancer patients to allow for simultaneous measurements of overall tumor pyruvate-to-lactate conversion parameters on mrs and glucose influx with 18f-fdg on pet. included patients are injected with a standard dose of radioactive 18f-fdg. subsequent dynamic pet acquisition is performed for up to 90 minutes after injection on an area-of-interest covering pre-specified tumor lesion(s). regional anatomical magnetic resonance imaging (mri) is performed, including diffusion weighted imaging (dwi) and contrast enhanced imaging (dce). mrs/mrsi is performed following the injection(s) of hyperpolarized \[1-13c\]pyruvate. when available, resected tumor tissues samples from surgical specimens or biopsies obtained in relation to routine clinical procedures will be collected and analyses of enzymes and markers of glycolytic metabolism will be performed ex vivo and compared with the in vivo data from pet/mrs.

Eligibility criteria:
inclusion criteria: * diagnosed with breast cancer, gastro-entero-pancreatic neuroendocrine neoplasms (gep-nen) grades g1, g2 or g3, lymphoma or sarcoma * measurable solid tumor of at least 1.5 cm * capable of understanding the patient information in danish and giving full informed consent exclusion criteria: * pregnancy * breast-feeding * weighs above 140 kg and/or with abdominal circumference exceeding the gantry of the pet/mr coil (120 cm) * history of allergic reaction attributable to compounds of similar chemical or biologic composition to 18f-fdg or pyruvate * patients who are unable to lie in the mr scanner for up to 90 minutes * pace-maker * metallic implantations within the past 6 weeks * non-mr compatible implants * claustrophobia * participants who have not fasted for a minimum of 4 hours prior to the planned scan time